Dr. Keller-Wood is currently an Assistant Research Scientist in the College of Medicine at the University of Florida. her primary research interest is control of the pituitary-adrenal axis, in particular the control of corticosteroid feedback, and the effect of pregnancy on regulation of this axis. She is pursuing this interest in her current grants. The research project which the candidate will be investigating involves control of ACTH during pregnancy. During pregnancy, plasma cortisol concentrations are elevated without the compensatory decrease in plasma ACTH concentrations that would be expected with cortisol feedback inhibition of ACTH. The proposed studies examine the control of basal and stress-induced ACTH secretion during pregnancy, in particular the interaction between cortisol and progesterone in control of ACTH, and the role of placental ACTH. The dose-response relation between plasma cortisol and both basal ACTH and ACTH responses to stress will be compared among ovariectomized nonpregnant ewes, ovariectomized nonpregnant ewes infused with progesterone, nonpregnant cycling ewes and pregnant ewes to determine if progesterone alters the dose-response curve between cortisol levels and inhibition of ACTH, and if such an effect accounts for altered cortisol-ACTH relations in pregnancy. ACTH responses to a variety of stimuli, including hypotensions, hypoglycemia and corticotropin-releasing factor, will also be compared among ovariectomized nonpregnant,nonpregnant progesterone-infused, and pregnant ewes to determine if progesterone during pregnancy alters ACTH response to stress. The contribution of placental ACTH to total ACTH secretion under basal and stimulated conditions will be calculated. These studies will lead to a better understanding of the normal physiology of the pituitary-adrenal system during pregnancy and may aid in understanding abnormal function in pregnancies complicated by Cushing's syndrome. Dr Keller-Wood plans further projects (including eventual renewal of the R01 on which this application is based) to explore interactions among stimuli during pregnancy, including changes in blood volume, pressure and glucose. The Department of Physiology includes several investigators whose interests involve the hormonal regulation of blood pressure and fluid volume. The University of Florida also has a strong program in perinatal physiology, including faculty in the Departments of Physiology, Pediatrics, and Obstetrics and Gynecology in the College of Medicine. This is therefore a strong, supportive environment in which the candidate will interact with more senior faculty. This RCDA award will give the candidate the financial support necessary to pursue her research interest as her sole focus in the next 5 years, and to develop her own strong, independent research program.